Non-injection mucosal vaccines are safe and convenient to use, and thus they have drawn attention as the next-generation vaccines. It was necessary to administer a mucosal vaccine simultaneously with a mucosal adjuvant in order to induce effective antigen-specific immune responses with the use of a mucosal vaccine. As mucosal adjuvants, toxin-related proteins, such as cholera toxins (CT) or detoxicated cholera toxins (mCT), are known. Addition of such mucosal adjuvants to mucosal vaccines enables transnasal vaccines to induce mucosal IgA in addition to antigen-specific systemic IgG. However, such mucosal adjuvant may disadvantageously migrate to the brain, and the safety thereof on organisms has remained problematic.
The present inventors developed nanogels comprising molecules such as cholesterol-bearing pulullan (CHP), which is composed of hydrophilic polysaccharides and hydrophobic cholesterol added thereto as a side chain, as DDS substrates (see WO 00/12564, JP Patent Publication (kokai) No. 2005-298644 A, WO 2006/049032, JP Patent Publication (kokai) No. 2006-143808 A, WO 2007/083643, JP Patent Publication (kokai) No. 2007-252304 A, and Hasegawa et al., Saibou Kougaku (Cell Technology), Vol. 26, No. 6, 2007, pp. 679-685). Specifically, CHP is capable of self-assembly in an aqueous environment, and it is converted into colloids (nanogels) with diameters of 20 to 30 nm capable of enclosing various substances therein. An excellent feature of CHP is the “molecular chaperone effects.” That is, upon enclosure of a molecule, such as a protein molecule, inside CHP nanogels, followed by release thereof, refolding takes place at the time of release, a physiological 3-D structure is formed, and normal activity is exerted.
While the use of such nanogels for vaccine preparations has been reported (see JP Patent No. 4033497), such nanogels become usable upon activation of cytotoxic T cells (CTL) for anti-cancer, anti-virus, or autoimmune disease treatment applications. That is, it could not be said that nanogels can always exert the effects of mucosal vaccines.
Also, use of a liposome having a lipid membrane comprising glycolipids and phospholipids for the delivery of oral vaccines had been reported (see JP Patent Publication (kokai) No. H05-339169 A (1993)).